Citation

Lamparello AJ, Namas RA, Abdul-Malak O, Vodovotz Y, Billiar TR. J. Am. Coll. Surg. 2019; 228(2): 148-160.e7.

Affiliation

Department of Surgery, University of Pittsburgh, Pittsburgh, PA; Center for Inflammation and Regenerative Modeling, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA. Electronic address: billiartr@upmc.edu.

Copyright

(Copyright © 2019, American College of Surgeons, Publisher Elsevier Publishing)

DOI

10.1016/j.jamcollsurg.2018.10.019

PMID

30448299

Abstract

BACKGROUND: Aging is accompanied by alterations in immune functions. How these changes translate into levels of circulating inflammatory mediators and network expression after severe trauma is not well characterized. To address this, we compared time-dependent changes in the levels of an extensive biomarker panel in cohorts of severely injured young and aged adults. STUDY DESIGN: Cohorts of young (18-30 years old, n=115) and aged (65-90 years old, n=101) blunt trauma patients admitted to the intensive care unit (ICU) with plasma sampled 3 times within the first 24 hours and daily from day (D)1 to D7 were assayed for 30 inflammatory biomarkers using Luminex™. Stringently matched groups controlling for sex ratio and injury severity score [ISS] (n = 56 young vs. n = 56 aged) were generated. Data were analyzed using 2-way ANOVA, area under the curve (AUC) analysis, Dynamic Bayesian Network (DyBN) inference, and Dynamic Network Analysis (DyNA).

RESULTS: In the overall cohorts, the young group had a significantly higher ISS, which was associated with higher circulating levels of 18 inflammatory mediators from admission to D7. The aged group had higher levels of C-X-C motif chemokine 10/interferon gamma-induced protein 10 (CXCL10/IP-10) and chemokine ligand 9/monokine induced by gamma interferon (CXCL9/MIG). In groups that were matched for ISS, the significantly higher levels of IP-10 and MIG persisted in the aged. DyBN revealed IP-10 and MIG as key mediators in the aged, while DyNA revealed higher network complexity in the aged.

CONCLUSIONS: These findings indicate that differences in the early inflammatory networks between young and aged trauma patients are not simply a suppression of pro-inflammatory responses in the aged, but are characterized by a major shift in the mediator profile patterns with high levels of CXC chemokines in the aged.

Copyright © 2018. Published by Elsevier Inc.

Language: en

Keywords

Biomarkers; Blunt Trauma; Dynamic Bayesian Network; Dynamic Network Analysis; Intensive Care Unit